tbuckley/cabot-search huggingface dataset:
Hippocampal neurons code individual episodic memories in humans
Authors: Luca D. Kolibius, Frederic Roux, George Parish, Marije Ter Wal, Mircea Van Der Plas, Ramesh Chelvarajah, Vijay Sawlani, David T. Rollings, Johannes D. Lang, Stephanie Gollwitzer, Katrin Walther, Rüdiger Hopfengärtner, Gernot Kreiselmeyer, Hajo Hamer, Bernhard P. Staresina, Maria Wimber, Howard Bowman, Simon Hanslmayr
Journal: Nature Human Behaviour (2023)

Abstract The hippocampus is an essential hub for episodic memory processing. However, how human hippocampal single neurons code multi-element associations remains unknown. In particular, it is debated whether each hippocampal neuron represents an invariant element within an episode or whether single neurons bind together all the elements of a discrete episodic memory. Here we provide evidence for the latter hypothesis. Using single-neuron recordings from a total of 30 participants, we show that individual neurons, which we term episode-specific neurons, code discrete episodic memories using either a rate code or a temporal firing code. These neurons were observed exclusively in the hippocampus. Importantly, these episode-specific neurons do not reflect the coding of a particular element in the episode (that is, concept or time). Instead, they code for the conjunction of the different elements that make up the episode.
Changing prevalence of chronic hepatitis B virus infection in China between 1973 and 2021: a systematic literature review and meta-analysis of 3740 studies and 231 million people
Authors: Zhenqiu Liu, Chunqing Lin, Xianhua Mao, Chengnan Guo, Chen Suo, Dongliang Zhu, Wei Jiang, Yi Li, Jiahui Fan, Ci Song, Tiejun Zhang, Li Jin, Catherine De Martel, Gary M Clifford, Xingdong Chen
Journal: Gut (2023)

Objective China concentrates a large part of the global burden of HBV infection, playing a pivotal role in achieving the WHO 2030 global hepatitis elimination target. Methods We searched for studies reporting HBV surface antigen (HBsAg) seroprevalence in five databases until January 2023. Eligible data were pooled using a generalised linear mixed model with random effects to obtain summary HBsAg seroprevalence. Linear regression was used to estimate annual percentage change (APC) and HBsAg prevalence in 2021. Results 3740 studies, including 231 million subjects, were meta-analysed. HBsAg seroprevalence for the general population decreased from 9.6% (95% CI 8.4 to 10.9%) in 1973–1984 to 3.0% (95% CI 2.1 to 3.9%) in 2021 (APC=−3.77; p&lt;0.0001). Decreases were more pronounced in children &lt;5 years (APC=−7.72; p&lt;0.0001) and 5–18 years (−7.58; p&lt;0.0001), than in people aged 19–59 years (−2.44; p&lt;0.0001), whereas HBsAg seroprevalence increased in persons ≥60 years (2.84; p=0.0007). Significant decreases were observed in all six major Chinese regions, in both men (APC=−3.90; p&lt;0.0001) and women (−1.82; p&lt;0.0001) and in high-risk populations. An estimated 43.3 million (95% uncertainty interval 30.7–55.9) persons remained infected with HBV in China in 2021 (3.0%), with notable heterogeneity by region (&lt;1.5% in North China to&gt;6% in Taiwan and Hong Kong) and age (0.3%, 1.0%, 4.7% and 5.6% for &lt;5 years, 5–18 years, 19–59 years and ≥ 60 years, respectively). Conclusions China has experienced remarkable decreases in HBV infection over the last four decades, but variations in HBsAg prevalence persist in subpopulations. Ongoing prevention of HBV transmission is needed to meet HBV elimination targets by 2030. Trial registration number PROSPERO (CRD42021284217)
COVID-19–Associated Hospitalizations Among U.S. Adults Aged ≥65 Years — COVID-NET, 13 States, January–August 2023
Authors: Christopher A. Taylor, Kadam Patel, Monica E. Patton, Arthur Reingold, Breanna Kawasaki, James Meek, Kyle Openo, Patricia A. Ryan, Anna Falkowski, Erica Bye, Kelly Plymesser, Nancy Spina, Brenda L. Tesini, Nancy E. Moran, Melissa Sutton, H. Keipp Talbot, Andrea George, Fiona P. Havers, Pam Daily Kirley, Isaac Armistead, Kimberly Yousey-Hindes, Nadine Oosmanally, Maya L. Monroe, Justin Henderson, Paige D’Heilly, Emily B. Hancock, Grant Barney, Sophrena Bushey, Laurie M. Billing, Nasreen Abdullah, William Schaffner, Emma Mendez
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Adults aged ≥65 years remain at elevated risk for severe COVID-19 disease and have higher COVID-19-associated hospitalization rates compared with those in younger age groups. Data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to estimate COVID-19-associated hospitalization rates during January-August 2023 and identify demographic and clinical characteristics of hospitalized patients aged ≥65 years during January-June 2023. Among adults aged ≥65 years, hospitalization rates more than doubled, from 6.8 per 100,000 during the week ending July 15 to 16.4 per 100,000 during the week ending August 26, 2023. Across all age groups, adults aged ≥65 years accounted for 62.9% (95% CI = 60.1%-65.7%) of COVID-19-associated hospitalizations, 61.3% (95% CI = 54.7%-67.6%) of intensive care unit admissions, and 87.9% (95% CI = 80.5%-93.2%) of in-hospital deaths associated with COVID-19 hospitalizations. Most hospitalized adults aged ≥65 years (90.3%; 95% CI = 87.2%-92.8%) had multiple underlying conditions, and fewer than one quarter (23.5%; 95% CI = 19.5%-27.7%) had received the recommended COVID-19 bivalent vaccine. Because adults aged ≥65 years remain at increased risk for COVID-19-associated hospitalization and severe outcomes, guidance for this age group should continue to focus on measures to prevent SARS-CoV-2 infection, encourage vaccination, and promote early treatment for persons who receive a positive SARS-CoV-2 test result to reduce their risk for severe COVID-19-associated outcomes.
Phenotyping by persistent inflammation in systemic sclerosis associated interstitial lung disease: a EUSTAR database analysis
Authors: Sabina Guler, Adela-Cristina Sarbu, Odile Stalder, Yannick Allanore, Vera Bernardino, Joerg Distler, Armando Gabrielli, Anna-Maria Hoffmann-Vold, Marco Matucci-Cerinic, Ulf Müller-Ladner, Vera Ortiz-Santamaria, Simona Rednic, Valeria Riccieri, Vanessa Smith, Susanne Ullman, Ulrich A Walker, Thomas K Geiser, Oliver Distler, Britta Maurer, Florian Kollert
Journal: Thorax (2023)

Systemic sclerosis (SSc) is a heterogeneous disease with frequently associated interstitial lung disease (SSc-ILD). We aimed to determine the prognostic potential of phenotyping patients with SSc and SSc-ILD by inflammation and to describe disease trajectories stratified by inflammation and immunosuppressive treatment.
No phenotypic or genotypic evidence for a link between sleep duration and brain atrophy
Authors: Anders M. Fjell, Øystein Sørensen, Yunpeng Wang, Inge K. Amlien, William F. C. Baaré, David Bartrés-Faz, Lars Bertram, Carl-Johan Boraxbekk, Andreas M. Brandmaier, Ilja Demuth, Christian A. Drevon, Klaus P. Ebmeier, Paolo Ghisletta, Rogier Kievit, Simone Kühn, Kathrine Skak Madsen, Athanasia M. Mowinckel, Lars Nyberg, Claire E. Sexton, Cristina Solé-Padullés, Didac Vidal-Piñeiro, Gerd Wagner, Leiv Otto Watne, Kristine B. Walhovd
Journal: Nature Human Behaviour (2023)

Abstract Short sleep is held to cause poorer brain health, but is short sleep associated with higher rates of brain structural decline? Analysing 8,153 longitudinal MRIs from 3,893 healthy adults, we found no evidence for an association between sleep duration and brain atrophy. In contrast, cross-sectional analyses (51,295 observations) showed inverse U-shaped relationships, where a duration of 6.5 (95% confidence interval, (5.7, 7.3)) hours was associated with the thickest cortex and largest volumes relative to intracranial volume. This fits converging evidence from research on mortality, health and cognition that points to roughly seven hours being associated with good health. Genome-wide association analyses suggested that genes associated with longer sleep for below-average sleepers were linked to shorter sleep for above-average sleepers. Mendelian randomization did not yield evidence for causal impacts of sleep on brain structure. The combined results challenge the notion that habitual short sleep causes brain atrophy, suggesting that normal brains promote adequate sleep duration—which is shorter than current recommendations.
CKD-EPI and EKFC GFR Estimating Equations: Performance and Other Considerations for Selecting Equations for Implementation in Adults
Authors: Lesley A. Inker, Hocine Tighiouart, Ogechi M. Adingwupu, Michael G. Shlipak, Alessandro Doria, Michelle M. Estrella, Marc Froissart, Vilmundur Gudnason, Anders Grubb, Roberto Kalil, Michael Mauer, Peter Rossing, Jesse Seegmiller, Josef Coresh, Andrew S. Levey
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement New eGFR equations from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) using creatinine (eGFRcr), cystatin C (eGFRcys), and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice, leading to uncertainty in selecting equations for implementation. The authors evaluated performance of equations in an independent population of 4050 adults and evaluated other considerations important for implementation. They found that CKD-EPI and EKFC equations are approaching convergence, with better performance of eGFRcr-cys equations in the overall group and fewer differences among race, sex, and age subgroups than eGFRcr equations. Larger differences among eGFRcr equations reflect regional population differences in creatinine, forcing a trade-off between accuracy and uniformity in global implementation of eGFRcr equations. More widespread use of cystatin C could avoid this trade-off. Background New CKD-EPI and EKFC eGFR equations using eGFRcr, eGFRcys, and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice. A better understanding of the equations, including their performance in race, sex and age subgroups, is important for selection of eGFR equations for global implementation. Methods We evaluated performance (bias and P 30 ) of equations and methods used for equation development in an independent study population comprising 4050 adults pooled from 12 studies. The mean (SD) measured GFR was 76.4 (29.6) ml/min per 1.73 m 2 and age 57.0 (17.4) years, with 1557 (38%) women and 579 (14%) Black participants. Results Coefficients for creatinine, cystatin C, age, and sex in the CKD-EPI and EKFC equations are similar. Performance of the eGFRcr-cys equations in the overall population (bias &lt;±5 ml/min per 1.73 m 2 and P 30 &gt;90%) was better than the eGFRcr or eGFRcys equations, with fewer differences among race, sex, and age subgroups. Differences in performance across subgroups reflected differences in diversity of source populations and use of variables for race and sex for equation development. Larger differences among eGFRcr equations reflected regional population differences in non-GFR determinants of creatinine. Conclusion CKD-EPI and EKFC equations are approaching convergence. It is not possible to maximize both accuracy and uniformity in selecting one of the currently available eGFRcr equations for implementation across regions. Decisions should consider methods for equation development in addition to performance. Wider use of cystatin C with creatinine could maximize both accuracy and uniformity of GFR estimation using currently available equations.
Intravenous Autologous Bone Marrow–derived Mesenchymal Stromal Cells Delay Acute Respiratory Distress Syndrome in Swine
Authors: Andriy I. Batchinsky, Teryn R. Roberts, Ben Antebi, Corina Necsoiu, Jae H. Choi, Maryanne Herzig, Andrew P. Cap, Jennifer S. McDaniel, Christopher R. Rathbone, Kevin K. Chung, Leopoldo C. Cancio
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit. Objectives: Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow–derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns. Methods: Yorkshire swine (n = 32, 44.3 ± 0.5 kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72 hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48 hours later, animals were randomized to receive autologous concentrated bone marrow aspirate (n = 10; 3 × 106 white blood cells and a mean of 56.6 × 106 platelets per dose), allogeneic MSCs (n = 10; 6.1 × 106 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals (n = 12). Measurements and Main Results: The intravenous administration of MSCs after injury and at 24 and 48 hours delayed the onset of ARDS in swine treated with autologous MSCs (48 ± 10 h) versus control animals (14 ± 2 h) (P = 0.004), reduced ARDS severity at 24 (P < 0.001) and 48 (P = 0.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72 hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-α (tumor necrosis factor-α). Conclusions: The intravenous administration of three doses of freshly processed autologous bone marrow–derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.
High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma
Authors: Katharine L. Lewis, Lasse H. Jakobsen, Diego Villa, Karin E. Smedby, Kerry J. Savage, Toby A. Eyre, Kate Cwynarski, Mark J. Bishton, Christopher P. Fox, Eliza A. Hawkes, Matthew J. Maurer, Tarec C. El-Galaly, Chan Y. Cheah, Sabela Bobillo, Paris L. Caporn, Joan Van Zyl, Magdalena Klanova, Marek Trněny, Robert Puckrin, Douglas A. Stewart, Aung M. Tun, Gita Thanarajasingam, Ranjit Nair, Loretta Nastoupil, Faouzi Djebbari, Erel Joffe, Sandra Eloranta, Sara Harrysson, Laurie H. Sehn, Seth M. Maliske, Kittika Poonsombudlert, Xiao Y. Guo, Greg Hapgood, Kate Manos, Jahanzaib Khwaja, Adrian Minson, Michael Dickinson, Andreas K. Øvlisen, Gareth P. Gregory, Michael Gilbertson, Isaac T. Streit, Hamish W. Scott, Matthew Ku, Sanjay de Mel, Kar Ying Yong, Liu Xin, Mridula Mokoonlall, Dipti Talaulikar, Nada Hamad, Sathia S. Srinivasan, Nicholas L. McVilly, Anna M. Johnston, Matthew J. Brunner, Priyanka A. Pophali
Journal: Journal of Clinical Oncology (2023)

PURPOSE CNS progression or relapse is an uncommon but devastating complication of aggressive B-cell lymphoma. There is no consensus regarding the optimal approach to CNS prophylaxis. This study was designed to determine whether high-dose methotrexate (HD-MTX) is effective at preventing CNS progression in patients at high risk of this complication. PATIENTS AND METHODS Patients age 18-80 years with aggressive B-cell lymphoma and high risk of CNS progression, treated with curative-intent anti–CD20-based chemoimmunotherapy, were included in this international, retrospective, observational study. Cause-specific hazard ratios (HRs) and cumulative risks of CNS progression were calculated according to use of HD-MTX, with time to CNS progression calculated from diagnosis for all patients (all-pts) and from completion of frontline systemic lymphoma induction therapy, for patients in complete response at completion of chemoimmunotherapy (CR-pts). RESULTS Two thousand four hundred eighteen all-pts (HD-MTX; n = 425) and 1,616 CR-pts (HD-MTX; n = 356) were included. CNS International Prognostic Index was 4-6 in 83.4% all-pts. Patients treated with HD-MTX had a lower risk of CNS progression (adjusted HR, 0.59 [95% CI, 0.38 to 0.90]; P = .014), but significance was not retained when confined to CR-pts (adjusted HR, 0.74 [95% CI, 0.42 to 1.30]; P = .29), with 5-year adjusted risk difference of 1.6% (95% CI, –1.5 to 4.4; all-pts) and 1.4% (95% CI, –1.5 to 4.1; CR-pts). Subgroups were underpowered to draw definitive conclusions regarding the efficacy of HD-MTX in individual high-risk clinical scenarios; however, there was no clear reduction in CNS progression risk with HD-MTX in any high-risk subgroup. CONCLUSION In this large study, high-risk patients receiving HD-MTX had a 7.2% 2-year risk of CNS progression, consistent with the progression risk in previously reported high-risk cohorts. Use of HD-MTX was not associated with a clinically meaningful reduction in risk of CNS progression.
Deciphering Evolutionary Trajectories of Lactate Dehydrogenases Provides New Insights into Allostery
Authors: Adeline Y Robin, Céline Brochier-Armanet, Quentin Bertrand, Caroline Barette, Eric Girard, Dominique Madern
Journal: Molecular Biology and Evolution (2023)

Lactate dehydrogenase (LDH, EC.1.1.127) is an important enzyme engaged in the anaerobic metabolism of cells, catalyzing the conversion of pyruvate to lactate and NADH to NAD+. LDH is a relevant enzyme to investigate structure-function relationships. The present work provides the missing link in our understanding of the evolution of LDHs. This allows to explain (i) the various evolutionary origins of LDHs in eukaryotic cells and their further diversification and (ii) subtle phenotypic modifications with respect to their regulation capacity. We identified a group of cyanobacterial LDHs displaying eukaryotic-like LDH sequence features. The biochemical and structural characterization of Cyanobacterium aponinum LDH, taken as representative, unexpectedly revealed that it displays homotropic and heterotropic activation, typical of an allosteric enzyme, whereas it harbors a long N-terminal extension, a structural feature considered responsible for the lack of allosteric capacity in eukaryotic LDHs. Its crystallographic structure was solved in 2 different configurations typical of the R-active and T-inactive states encountered in allosteric LDHs. Structural comparisons coupled with our evolutionary analyses helped to identify 2 amino acid positions that could have had a major role in the attenuation and extinction of the allosteric activation in eukaryotic LDHs rather than the presence of the N-terminal extension. We tested this hypothesis by site-directed mutagenesis. The resulting C. aponinum LDH mutants displayed reduced allosteric capacity mimicking those encountered in plants and human LDHs. This study provides a new evolutionary scenario of LDHs that unifies descriptions of regulatory properties with structural and mutational patterns of these important enzymes.
Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trial
Authors: Mazen Noureddin, Shaharyar Khan, Francisco Portell, Diane Jorkasky, Jameel Dennis, Omer Khan, Lars Johansson, Edvin Johansson, Arun J Sanyal
Journal: The Lancet. Gastroenterology & hepatology (2023)
Dopamine in the nucleus accumbens shell controls systemic glucose metabolism via the lateral hypothalamus and hepatic vagal innervation in rodents
Authors: Charlene Diepenbroek, Merel Rijnsburger, Astrid A.S. van Irsen, Leslie Eggels, Alexandre Kisner, Ewout Foppen, Unga A. Unmehopa, Chloé Berland, Sophie Dólleman, Marene Hardonk, Céline Cruciani-Guglielmacci, Rudolf P. Faust, Rick Wenning, Clarissa M. Maya-Monteiro, Andries Kalsbeek, Yeka Aponte, Serge Luquet, Mireille J.M. Serlie, Susanne E. la Fleur
Journal: Metabolism (2023)

Growing evidence demonstrates the role of the striatal dopamine system in the regulation of glucose metabolism. Treatment with dopamine antagonists is associated with insulin resistance and hyperglycemia, while dopamine agonists are used in treatment of type 2 diabetes. The mechanism underlying striatal dopamine effects in glucose metabolism, however is not fully understood. Here, we provide mechanistic insights into the role of nucleus accumbens shell (sNAc) dopaminergic signaling in systemic glucose metabolism.Endogenous glucose production (EGP), blood glucose and mRNA expression in the lateral hypothalamic area (LHA) in male Wistar rats were measured following infusion of vanoxerine (VNX, dopamine reuptake inhibitor) in the sNAc. Thereafter, we analyzed projections from sNAc Drd1-expressing neurons to LHA using D1-Cre male Long-Evans rats, Cre-dependent viral tracers and fluorescence immunohistochemistry. Brain slice electrophysiology in adult mice was used to study spontaneous excitatory postsynaptic currents of sNAc Drd1-expressing neurons following VNX application. Finally, we assessed whether GABAergic LHA activity and hepatic vagal innervation were required for the effect of sNAc-VNX on glucose metabolism by combining infusion of sNAc-VNX with LHA-bicuculline, performing vagal recordings and combining infusion of sNAc-VNX with hepatic vagal denervation.VNX infusion in the sNAc strongly decreased endogenous glucose production, prevented glucose increases over time, reduced Slc17A6 and Hcrt mRNA in LHA, and increased vagal activity. Furthermore, sNAc Drd1-expressing neurons increased spontaneous firing following VNX application, and viral tracing of sNAc Drd1-expressing neurons revealed direct projections to LHA with on average 67 % of orexin cells directly targeted by sNAc Drd1-expressing neurons. Importantly, the sNAc-VNX-induced effect on glucose metabolism was dependent on GABAergic signaling in the LHA and on intact hepatic vagal innervation.We show that sNAc dopaminergic signaling modulates hepatic glucose metabolism through GABAergic inputs to glutamatergic LHA cells and hepatic vagal innervation. This demonstrates that striatal control of glucose metabolism involves a dopaminergic sNAc-LHA-liver axis and provides a potential explanation for the effects of dopamine agonists and antagonists on glucose metabolism.
68Ga-FAPI and 18F-FDG PET/CT in Intravenous Leiomyomatosis
Authors: Zhuoyuan Li, Dan Su, Yue Chen
Journal: Clinical Nuclear Medicine (2023)

Intravenous (IV) leiomyomatosis is a rare IV disease. Our case presents 68 Ga-FAPI and 18 F-FDG PET/CT findings of IV leiomyomatosis in a 37-year-old woman. Intravenous leiomyomatosis shows only mild FDG but intense 68 Ga-FAPI activity on PET/CT studies. In this case, 68 Ga-FAPI was superior to 18 F-FDG PET/CT in detecting IV leiomyomatosis.
Vitamins and Hormone Therapy for Coronary Atherosclerosis—Reply
Authors: David D. Waters
Journal: JAMA (2003)

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